| Description |
A947 is a potent and selective SMARCA2 proteolysis-targeting chimera molecule (PROTAC). A947 also is a potent and moderately selective SMARCA2 degrader. A947 has binding affinity to the SMARCA2 bromodomain with a Kd value of 93 nM. A947 can be used for the research of cancer[1].
|
| Related Catalog |
|
| Target |
Kd: 93 nM (SMARCA2), 65 nM (SMARCA4); DC50 for SMARCA2: 39 pM (in SW1573 cells)[1].
|
| In Vitro |
A947 has binding affinity to the SMARCA2 and SMARCA4 bromodomains with Kd values of 93 nM and 65 nM, respectively[1]. A947 can potently degrade SMARCA2 in SW1573 cells with a DC50 value of 39 pM[1]. A947 (100 nM, 500 nM) mediates ubiquitination and degradation of SMARCA2/4[1]. A947 (0-500 nM) can inhibit growth of SMARCA4-mutant NSCLC cells[1]. Western Blot Analysis[1] Cell Line: SW1573 cells Concentration: 0-10 nM Incubation Time: 18 h Result: Degraded SMARCA2 with amaximal degradation of 96% in 10 nM. Cell Viability Assay[1] Cell Line: NCI-H1944 cells Concentration: 0-500 nM Incubation Time: 7 days Result: Showed the dose-dependent inhibition of growth. Cell Cycle Analysis[1] Cell Line: HCC2302, NCI-H1793, RERF-LC-AI, NCI-H1944, Calu-6, NCI-H460, A427 cells Concentration: 0-500 nM Incubation Time: 48 h Result: Showed G1 arrest in SMARCA4mut models. Apoptosis Analysis[1] Cell Line: NCI-H1944, NCI-H838 cells Concentration: 100 nM Incubation Time: 50 h Result: Induced cells toward apoptotic cell death.
|
| In Vivo |
A947 (i.v.; 40 mg/kg; single-dose, 2 week or every other week, 30 days) has active in SMARCA4-mutant NSCLC xenograft models in vivo[1]. Animal Model: SMARCA4-mutant NSCLC xenograft models Dosage: 40mg/kg Administration: Intravenous , single-dose, 2 week; Intravenous , every other week, 30 days Result: Rapidly reduced the tumor SMARCA2 protein levels and significant decreased the tumor growth.
|
| References |
[1]. Jennifer Cantley, et al. Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat Commun. 2022 Nov 10;13(1):6814.
|
